Counseling regarding heart disease risk and statin use for women with HIV should emphasize that the risks are similar for men and women with HIV when communicating the results of the REPRIEVE study. One of the study’s researchers spoke at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) last week in Denver.

Advice is also needed to make women aware of how heart disease symptoms differ between women and men.

Dr. Markella Zani, Director of Women’s Health Research in the Department of Metabolism at Massachusetts General Hospital in Boston, presented a summary of insights from the REPRIEVE trial regarding sex differences in cardiovascular risk among people with HIV.

The REPRIEVE study of pitavastatin for the prevention of cardiovascular disease showed that statins reduced the risk of major cardiovascular events such as heart attack and stroke to a similar extent (about 35%) in men and women. . The study recruited people with HIV who were at low to moderate risk for cardiovascular disease based on age, cholesterol levels, and other key risk factors.

However, this study revealed unexpected levels of cardiovascular risk, particularly among HIV-infected women in high-income countries.

In the general population, women are estimated to have lower cardiovascular risk than men. In fact, in the REPRIEVE study, the 10-year average cardiovascular risk score at study entry was 1.9% for women and 5.4% for men, even though the median ages of male and female participants were similar. . Women in the study were less likely to smoke than men but more likely to have high blood pressure, and a higher proportion were black or African American.

However, when the incidence of major cardiovascular events was compared in four strata from <2.5% to ≥10% of baseline cardiovascular risk, women had the same event rates as men. In the highest-risk strata, there was a strong trend toward higher rates of serious events among women. After adjusting for other risk factors, female sex at birth was not protective against major cardiovascular events in the overall study population.

Cardiovascular risk scores underpredicted cardiovascular event rates among women and trial participants from high-income countries. In women, the incidence of events exceeded the predicted number by 42%. For participants from high-income countries, the event rate was 30% higher than expected. The discrepancy between predicted and actual events was most pronounced in women from high-income countries, for whom the cardiovascular event rate was 2.5 times higher than predicted by the score.

Dr. Zanni said the REPRIEVE findings should change the way HIV-infected women are counseled about cardiovascular risk and statin therapy, especially in high-income settings. New guidelines from the UK and US recommend statin treatment for people with HIV, although their weight varies. UK guidelines recommend statins for all HIV-infected people over 40 years of age, regardless of cardiovascular risk, whereas US guidelines recommend statins for people over 40 years of age with less than 5% cardiovascular risk. Discussion of whether to start statin therapy is recommended for people with HIV infection. HIV-related factors that may increase risk should be considered.

While discussions about the risk of heart disease in the general population may state that women have a lower risk of heart disease than men, this does not seem to be the case for women with HIV.

Doctors should also encourage women with HIV to discuss potential symptoms of heart disease, Dr. Zanni said. Signs of heart disease and heart attack may be different in women. According to the American Heart Association, shortness of breath, nausea, vomiting, and back and jaw pain are common but often overlooked symptoms in women.

Why are women with HIV at the same risk of heart disease as men? Women have a stronger innate immune response to HIV than men, resulting in greater immune activation. Inflammation and immune activation promote the development of plaque, a buildup of fat that blocks arteries.

The reproductive hormone estrogen influences several pathways in the development of heart disease, and decreased estrogen production during menopause increases cardiovascular risk. Baseline analysis of REPRIEVE participants found that increasing reproductive age was associated with increased immune activation and increased waist circumference. Gaining weight also increases blood pressure, which is a significant risk factor for heart disease.

“We need to think about mitigating the immune activation and weight gain associated with the reproductive age transition,” Dr. Zanni says.

Further research is needed to understand whether the mechanisms contributing to heart disease in HIV-infected individuals differ by gender and how statins influence these pathways. Dr. Zani said at the conference that plaques that do not cause symptoms of heart disease may have a greater impact on a woman’s risk of heart disease. Also, plaque may not be the only factor determining a woman’s risk of heart disease. Malfunction of the small blood vessels that serve the heart can also increase the risk of heart disease. Both possibilities are being investigated with REPRIEVE study participants.